CRIPTO is a 188 aa protein shares homologies with the epidermal growth factor (EGF) family (EMBO Journal (1989) Vol 8 (7) pp1987-1991).
huCRIPTO mRNA is detected only in undifferentiated cells and disappear after cell differentiation mCRIPTO is expressed during pregnancy and lactation (induces branching morphogenesis in mammary epithelial cells) and is suspected to be an autocrine growth factor for normal breast cells. CRIPTO is required for correct orientation of the anterior-posterior axis in the mouse embryo.
Human cripto gene has been expressed U.S. Pat. No. 5,654,140.
Cancer is a significant health problem throughout the world. Although advances have been made in detection and therapy of cancer, no vaccine or other universally successful method for prevention and/or treatment is currently available. Current therapies, which are generally based on a combination of chemotherapy or surgery and radiation, continue to prove inadequate in many patients.
Colon cancer is the second most frequently diagnosed malignancy in the United Sates as well as the second most common cause of cancer death. An estimated 95,600 new cases of colon cancer will have been diagnosed in 1998, with an estimated 47,700 deaths. The five-year survival rate for patients with colorectal cancer detected in an early-localised stage is 92%, unfortunately, only 37% of colorectal cancer is diagnosed at this stage. The survival stage. The survival rate drops to 64% if the cancer is allowed to spread to adjacent organs or lymph nodes, and to 7% in patients with distant metastases.
The prognosis of colon cancer is directly related to the degree of penetration of the tumour through the bowel wall, to the level of metastasis, to the presence or absence of nodal involvement, consequently, early detection and treatment are especially important. Currently, diagnosis is aided by the use of screening assays for fecal occult blood, sigmoidoscopy, colonoscopy and double contrast barium enemas. Treatment regimens are determined by the type and stage of the cancer, and include surgery, radiation therapy and/or chemotherapy. Recurrence following surgery (the most common form of therapy) is a major problem and is often the ultimate cause of death. In spite of considerable research into therapies for the disease, colon cancer remains difficult to diagnose and treat. Accordingly, there is a need in the art for improved methods for treating such cancers. The present invention fulfils these needs and further provides other related advantages.
Breast cancer is a significant health problem for women in the United States and throughout the world. Although advances have been made in detection and treatment of the disease, breast cancer remains the second leading cause of cancer-related deaths in women, affecting more than 180,000 women in the United States each year. For women in North America, the lifetime odds of getting breast cancer are now one in eight.
No vaccine or other universally successful method for the prevention or treatment of breast cancer is currently available. Management of the disease currently relies on a combination of early diagnosis (through routine breast screening procedures) and aggressive treatment which may including one or more of a variety of treatments such as surgery, radiotherapy, chemotherapy and hormone therapy. The course of treatment for a particular breast cancer is often selected based on a variety of prognostic parameters, including an analysis of specific tumour markers. See, eg Porter-Jordan and Lippman, Breast Cancer 8:73-100 (1994). However, the use of established markers often leads to a result that this is difficult to interpret, and the high mortality observed in breast cancer patients indicates that improvements are needed in the treatment and prevention of the disease.
Lung cancer is the primary cause of cancer death among both men and women in the US, with an estimated 172,000 new cases being reported in 1994. The five-year survival rate among all lung cancer patients, regardless of the state of disease at diagnosis is only 13%. This contrasts with a five-year survival rate of 46% among cases detected while the disease is still localised. However, only 16% of lung cancers are discovered before the disease has spread.
In spite of considerable research into therapies for these and other cancers, breast, colon and colorectal remains difficult to diagnose and treat effectively. Accordingly, there is a need in the art for improved methods for treating and preventing such cancers. The present invention fulfills these needs and further provides other related advantages.